Iodine-induced synthesis of sulfonate esters from sodium sulfinates and phenols under mild conditions

Article abstract of DOI:10.1039/c5ra00724k

An iodine-induced synthesis of sulfonate esters via cross-coupling reactions of sodium sulfinates with phenols is reported. This synthetic route is low-cost, facile, green and efficient, and could afford the target products with good to excellent yields u

Full text of DOI:10.1039/c5ra00724k

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Iodine-induced synthesis of sulfonate esters from
sodium sulfinates and phenols under mild
conditions†
Cite this: RSC Adv., 2015, 5, 27439
Received 13th January 2015
Accepted 12th March 2015
*
Jian Gao, Xiaojun Pan, Juan Liu, Junyi Lai, Liming Chang and Gaoqing Yuan
DOI: 10.1039/c5ra00724k
www.rsc.org/advances
An iodine-induced synthesis of sulfonate esters via cross-coupling readily available and eco-friendly.16 Recently, some interesting
reactions of sodium sulfinates with phenols is reported. This reactions related phenols in organic chemistry have been also
synthetic route is low-cost, facile, green and efficient, and could afford reported.17
the target products with good to excellent yields under mild
Based on our research interest in iodine-mediated reac-
tions,18 herein we reported an iodine-induced the synthesis of
sulfonate esters from sodium sulnates and phenols under
mild conditions. To our knowledge, such a route for the
synthesis of sulfonate esters has not been reported to date.
To optimize the reaction conditions, the reaction of
4-chlorophenol (1a) with sodium p-toluenesulnate (2a) was
selected as the model reaction, and the results were shown in
Table 1. When the reaction of 1a and 2a was carried out in the
presence of I2 in CH3CN for 5 h, the yield of 4-chlorophenyl
4-methylbenzenesulfonate (3a) was only 10% (entry 1). Pinhey's
investigations indicated that base additives could efficiently
promote the coupling reaction of phenols with aryllead triace-
tates.19 Based on this idea, we suppose that base may act as the
similar role in the present system. Thus, we examined the effect
of various inorganic and organic bases on the coupling reaction
of 4-chlorophenol with sodium p-toluenesulnate. In the pres-
ence of CH3COONa, the yield of 3a was raised to 36% (entry 2).
Very pleasedly, Cs2CO3, especially K2CO3, could dramatically
improve the yield of 3a (entries 3 and 4). However, a strong
conditions.
Sulfonate esters are well-known ester compounds and crucial
pharmaceutical ingredients which work as bridge structures or
ligands and have presented particular biological activities (such
as antitumor and monoamine oxidase inhibitory activities) in
medicinal chemistry (Fig. 1).1–4 Besides, sulfonate esters play a
unique role in coupling reactions because sulfonate ester
groups are removed easily.5 To date, many methods have been
developed to synthesize sulfonate esters, mainly including the
reaction of phenols with sulfonic acids,6 or with thiols using
H2O2–POCl3 system,7 and with sulfonyl chlorides in ionic
liquids,8 or under microwave-assistance9 and catalyzed by
copper oxide.10 Other routes have been also reported.11 Never-
theless, most of these methods suffer from harsh reaction
conditions. In addition, expensive and unstable sulfonyl chlo-
rides as sulfonylating reagents would lead to some drawbacks.
Hence, it is necessary to search for low-cost, green and efficient
sulfonylating reagents (sulfonyl sources) for the synthesis of
sulfonate esters.
In recent years, many chemists became interested in the
direct sulfonylation reaction using various sulfonylation
reagents.12 Among various sulfonylation reagents, sodium sul-
nates seem to be more attractive due to their stability, low
price and convenience handling. Actually, sodium sulnates
have been widely applied in sulfonylations,13 C–H arylations14
and sulfenylations.15 In addition, iodine-mediated synthesis has
attracted more and more attention because iodine is cheap,
School of Chemistry and Chemical Engineering, South China University of Technology,
Guangzhou, 510640, P. R. China. E-mail: gqyuan@scut.edu.cn
† Electronic supplementary information (ESI) available: Detailed experimental
procedures, characterization of products, and NMR spectral charts. See DOI:
10.1039/c5ra00724k
Fig.
1 Selected examples for bioactive and pharmaceutical
compounds containing sulfonate ester group.
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Table 1 Optimization of reaction conditionsa
Table 2 Synthesis of sulfonate esters with various phenolsa,b
Entry
Base
Solvent
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
No base
CH3COONa
Cs2CO3
K2CO3
KOH
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3OH
H2O
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
5
10
36
80
98
19
6
14
98
11
57
75
69
94
89
Trace
Trace
77
Et3N
Pyridine
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
9
10
11
12
13c
14d
15e
16f
17g
18h
19i
DMF
EtOH
DMSO
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
a
Reaction conditions: 1 (0.5 mmol), 2a (0.6 mmol), I2 (0.5 mmol), K2CO3
(1 equiv.), CH3OH (2 mL), room temperature. b Isolated yield based on 1.
90
88
c
d
CH3CN (2 mL) as the solvent. Using CH3ONa (0.5 mmol) instead of
K2CO3.
a
Reaction conditions: 1a (0.5 mmol), 2a (0.6 mmol), I2 (1 equiv.), base
b
(1 equiv.), solvent (2 mL) and room temperature. GC yield based on
c
d
e
1a. At 50 ꢀC. Reaction in a dark background. Adding TEMPO.
f
g
Adding BHT. Using tosyl iodide (0.6 mmol) instead of 2a and I2.
h
Under N2 atmosphere. i Reaction on a 10 mmol scale.
that the presence of electron-donating groups is not favourable
for the conversion of phenols to aryloxy anion. In the present
reaction system, the aryloxy anion may be one of key interme-
diates. To our delight, naphthol and quinolin-8-ol performed
with good yields (3m–3o). Specially, aliphatic alcohols could
react well with sodium p-toluenesulnate (2a) in CH3CN solvent
to afford the target products (3p–3r) with good yields when
K2CO3 was replaced by CH3ONa. These results indicate that
aliphatic alcohols are also suitable for this transformation in
the presence of a strong base CH3ONa.
On the other hand, the reactions of some sodium sulnates
with 1a were examined, and the result was summarized in Table
3. Various sodium sulnates with 4-uoro, 4-chloro, 4-bromo,
4-methoxyl and 4-ethyl groups substituted on aryl rings all
proceeded smoothly to give good to excellent yields (3s–3x). In
addition, 4-chlorophenylphenylmethane sulfonate (3y) was also
obtained in a high yield.
To investigate the reaction mechanism, several controlled
experiments were performed (Table 1, entries 14–18). Firstly,
when radical scavenger TEMPO or BHT was added to this
reaction system (Table 1, entries 15 and 16), no desired 3a was
obtained, indicating that the reaction involves a radical
pathway. Besides, when the reaction of tosyl iodide instead of
molecule iodine with 2a was carried out (Table 1, entry 17), 3a
was still obtained in a high yield, revealing that tosyl iodide may
be an intermediate in this transformation. Even if the reaction
was proceeded in a dark background or under N2 atmosphere,
the yield of 3a was almost unchanged (Table 1, entries 14 and
18). This means that visible light and oxygen were irrelevant for
this transformation. As a result, a possible mechanism is
inorganic base KOH and organic bases (Et3N and pyridine) gave
unsatisfactory results (entries 5–7). The effect of solvents were
further investigated. Compared with other solvents (H2O, DMF,
EtOH and DMSO), CH3CN or CH3OH gave the better results
(entries 8–12). Considering the toxicity of CH3CN, we chose
CH3OH as the solvent for this transformation. When the
temperature was elevated to 50 ꢀC, the yield of 3a was not
inuenced (entry 13), so room temperature was found as the
optimal temperature. In addition, the amount of I2 and K2CO3
has a great inuence on the reaction (see ESI†). When 1 equiv.
of I2 or K2CO3 was used in the present system, the best result
could be obtained (entry 8). Moreover, when the reaction was
performed on a 10.0 mmol scale (Table 1, entry 19), an excellent
yield (88%) of 3a was obtained. This means that the reaction
could be scalable and has a potential application for the prep-
aration of more complex molecules.
Under the optimized reaction conditions, the scope of
synthesis of sulfonate esters by using various phenols with 2a
was investigated (Table 2). A series of ortho and para-substituted
phenols by electron-withdrawing groups (R ¼ F, Br, I, NO2, CN)
all proceeded smoothly to afford the corresponding products
(3d–3f, 3i–3k) in excellent yields. However, when some electron-
donating groups (R ¼ CH3, isopropyl) substituted phenols were
used, a long reaction time was needed, a lower yield was
obtained, and some by-products substituted by iodine were
observed (3c, 3g, 3h, 3l). This result may be attributed to the fact
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Table 3 Scope of various sodium sulfonatesa,b
Scheme 2 A total reaction equation for this transformation.
Sodium sulnate
Product
Yield (%)
86
In conclusion, we have developed a simple, metal-free and
eco-friendly synthesis of sulfonate esters from sodium sul-
nates and phenols. Compared with the reported methods (such
as using sulfonyl chlorides as starting materials), the present
route appears to be more attractive and efficient for the
synthesis of sulfonate esters. Further study on this reaction's
application is ongoing currently in our laboratory.
3s
3t
90
3u
3v
88
89
74
Acknowledgements
We are grateful to the National Natural Science Foundation of
China (21172079) and the Science and Technology Planning
Project of Guangdong Province (2011B090400031) for nancial
support.
3w
3x
3y
77
82
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